Hypocretin/orexin neurons encode social discrimination and exhibit a sex-dependent necessity for social interaction
Matthew Dawson,
Dylan J. Terstege,
Naila Jamani,
Mio Tsutsui,
Dmitrii Pavlov,
Raluca Bugescu,
Jonathan R. Epp,
Gina M. Leinninger,
Derya Sargin
Affiliations
Matthew Dawson
Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
Dylan J. Terstege
Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
Naila Jamani
Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
Mio Tsutsui
Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
Dmitrii Pavlov
Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada
Raluca Bugescu
Department of Physiology, Michigan State University, East Lansing, MI, USA
Jonathan R. Epp
Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada; Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
Gina M. Leinninger
Department of Physiology, Michigan State University, East Lansing, MI, USA
Derya Sargin
Department of Psychology, University of Calgary, Calgary, AB, Canada; Department of Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada; Corresponding author
Summary: The hypothalamus plays a crucial role in the modulation of social behavior by encoding internal states. The hypothalamic hypocretin/orexin neurons, initially identified as regulators of sleep and appetite, are important for emotional and motivated behaviors. However, their role in social behavior remains unclear. Using fiber photometry and behavioral analysis, we show here that hypocretin neurons differentially encode social discrimination based on the nature of social encounters. The optogenetic inhibition of hypocretin neuron activity or blocking of hcrt-1 receptors reduces the amount of time mice are engaged in social interaction in males but not in females. Reduced hcrt-1 receptor signaling during social interaction is associated with altered activity in the insular cortex and ventral tegmental area in males. Our data implicating hypocretin neurons as sexually dimorphic regulators within social networks have significant implications for the treatment of neuropsychiatric diseases with social dysfunction, particularly considering varying prevalence among sexes.
